Safety, Pharmacokinetics and Pharmacodynamics of BEZ235 Plus MEK162 in Selected Advanced Solid Tumor Patients

Pfizer29 enrolled

Overview

This is an open label, dose finding, phase Ib clinical trial to determine the maximum tolerated dose (MTD) and/or RP2D of the orally administered PI3K/mTOR inhibitor BEZ235 in combination with the MEK1/2 inhibitor MEK162. This combination will be explored in patients with EGFR mutant NSCLC which has progressed on EGFR inhibitors and triple negative breast cancer, as well as pancreatic cancer, colorectal cancer, malignant melanoma, NSCLC, and other advanced solid tumors with KRAS, NRAS, and/or BRAF mutations. Dose escalation will be guided by a Bayesian logistic regression model with overdose control. At MTD or RP2D, two expansion arms will be opened in order to further assess safety and preliminary anti-tumor activity of the combination of BEZ235 and MEK162. Study drugs will be administered orally on a continuous schedule, MEK162 bid and BEZ235 qd, a treatment cycle is defined as 28 days.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Unspecified Adult Solid Tumor, Protocol Specific Solid Tumor

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * histologically/cytologically confirmed, advanced non resectable solid tumors * Measurable or non-measurable, but evaluable disease as determined by RECIST 1.0 Exclusion Criteria: * Patients with primary CNS tumor or CNS tumor involvement * Diabetes mellitus - Unacceptable ocular/retinal conditions Other protocol-defined inclusion/exclusion criteria may apply

Locations (6)

Massachusetts General Hospital Mass General 2

Boston, Massachusetts, United States

University of Texas/MD Anderson Cancer Center MD Anderson PSC

Houston, Texas, United States

Pfizer Investigative Site

Parkville, Victoria, Australia

Pfizer Investigative Site

Toronto, Ontario, Canada

Pfizer Investigative Site

Villejuif, France

Pfizer Investigative Site

Barcelona, Catalonia, Spain

Outcomes

Primary Outcomes

Incidence of Dose Limiting Toxicities

A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination

Time frame: during Cycle 1 of treatment with BEZ235 and MEK162

Secondary Outcomes

Number of participants with adverse events and serious adverse events

A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination

Time frame: from Cycle 1 Day 1 until treatment discontinuation

Overall response rate, duration of response, time to response and progression free survival

Time frame: every 8 weeks of treatment

Time versus plasma concentration profiles of BEZ235 and MEK162

A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination

Time frame: during the first cycle of treatment

Treatment-induced PI3K and MEK/ERK pathway signaling inhibition and evidence of biological activity in tumor

A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination

Time frame: during the first cycle of treatment and at disease progression